Protein Design and its Application in Bionanotechnology and Synthetic Biology
The primary basic research interest of the group is the informational aspect of the protein-folding problem; that is, how does the sequence of a protein determine its active, three-dimensional structure or fold?
We tackle this problem using the following multi-disciplinary approach:
We are interested in the folding and assembling of a number of protein-folding motifs, including zinc fingers and beta-structured proteins. However, our recent interest has focused the coiled-coil motif.
Coiled coils are protein-folding motifs that direct and cement a wide variety of protein-protein interaction throughout biology. They comprise two or more alpha-helices that wrap around one another to form helical ropes. Despite their apparent simplicity, these structures are ubiquitous and account for between 5-10% of all coding DNA sequence.
The bioinformatics challenge is to decipher rules within coiled-coil sequences that determine the different structures that are possible, and discriminate between different coiled-coil partners. It is these motifs and, more importantly, the sequence-to-structure rules that underlie them that the group examines and uses in de novo design.
Emily Baker (with Charl Faul), Gail Bartlett, Marc Bruning, Berti Chi (with Paula Booth), Orhan Ertughrul, Jordan Fletcher (with Paula Booth), Leyla Hussein (with Leo Brady), Nazia Mehrban, Franziska Mende, John Simms (with Paula Booth), and Drew Thomson.
NR Zaccai, B Chi, AR Thomson, AL Boyle, GJ Bartlett, M Bruning, N Linden, RB Sessions, PJ Booth, RL Brady, DN Woolfson. (2011) A de novo peptide hexamer with a mutable channel. Nature Chemical Biology. 7: 935-941.
A Yoshizumi, JM Fletcher, Z Yu, A Persikov, GJ Bartlett, AL Boyle, TL Vincent, DN Woolfson, B Brodsky. (2011) Designed coiled coils promote folding of a recombinant bacterial collagen. Journal of Biological Chemistry. 286: 1715-1720.
GJ Bartlett, A Choudhary, RT Raines, DN Woolfson. (2010) n-->pi* interactions in proteins. Nature Chemical Biology. 6: 567-568.
EF Banwell, ES Abelardo, DJ Adams, MA Birchall, A Corrigan, AM Donald, M Kirkland, LC Serpell, MF Butler, DN Woolfson. (2009) Rational design and application of responsive alpha-helical peptide hydrogels. Nature Materials. 8: 596-600.